合成、抗惊厥和神经毒性评价一些新的嘧啶-5-腈衍生物。
Synthesis, anticonvulsant and neurotoxicity evaluation of some new pyrimidine-5-carbonitrile derivatives.
机构信息
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110 062, India.
出版信息
Saudi Pharm J. 2012 Apr;20(2):149-54. doi: 10.1016/j.jsps.2011.09.007. Epub 2011 Sep 24.
Abstract
A series of 2-[2-(substituted benzylidene) hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (3-16) were synthesized by refluxing 2-hydrazino-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (2) with different substituted aromatic aldehydes in glacial acetic acid and absolute alcohol mixture (8:2). The compounds were evaluated for their anticonvulsant and neurotoxicity effect. In MES test compounds 2-[2-(4-bromo-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (5), 2-[2-(4-hydroxy-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (9), and 2-[2-(3-fluoro-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (16) were found to be highly active at a dose level of 30 mgkg(-1) at 0.5 h time interval, indicating their ability to prevent seizure spread at a relatively low dose.
摘要
一系列 2-[2-(取代苄叉基)腙基]-4-(4-甲氧基苯基)-6-氧代-1,6-二氢嘧啶-5-甲腈（3-16）是通过将 2-肼基-4-(4-甲氧基苯基）-6-氧代-1,6-二氢嘧啶-5-甲腈（2）与不同取代的芳醛在冰醋酸和无水乙醇的混合物（8:2）中回流合成的。这些化合物被评估了它们的抗惊厥和神经毒性作用。在 MES 测试中，化合物 2-[2-(4-溴苄叉基）-肼基]-4-(4-甲氧基苯基）-6-氧代-1,6-二氢嘧啶-5-甲腈（5）、2-[2-(4-羟基苄叉基）-肼基]-4-(4-甲氧基苯基）-6-氧代-1,6-二氢嘧啶-5-甲腈（9）和 2-[2-(3-氟苄叉基）-肼基]-4-(4-甲氧基苯基）-6-氧代-1,6-二氢嘧啶-5-甲腈（16）在 30 mgkg(-1)的剂量水平下，在 0.5 h 的时间间隔内表现出高度活性，表明它们能够以相对较低的剂量防止癫痫发作的扩散。
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